METHODS: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility.
RESULTS: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35.6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62.3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19.7%). One hundred and fifty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors = 75; immunotherapy = 4). Median duration of immunotherapy and poly ADP ribose polymerase were 20.5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53% (n = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71).
CONCLUSIONS: One-third of cancer patients tested carried a PGV and ∼80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics.
方法:我们对在我们中心接受种系基因检测的患者进行了回顾性研究,以确定可操作致病性种系变异(PGV)的患病率及其临床应用。
结果:从2000年到2022年,1154名癌症患者接受了种系测试,大多数(945/1154)使用多基因面板进行了测试。41111名(35.6%)患者患有PGV,334名(81%)具有临床可行性。BRCA1/2占可操作突变的62.3%,其次是错配修复(18%),和其他同源重组修复(HRR)基因(19.7%)。一百五十二名种系阳性患者患有晚期癌症,79例接受了种系定向治疗(聚ADP核糖聚合酶抑制剂=75;免疫疗法=4).免疫治疗和多聚ADP核糖聚合酶的中位持续时间为20.5个月(范围5-40个月)和8个月(范围1-76个月),分别。在接受铂类化疗的BRCA/HRR突变携带者中,新辅助治疗组的病理完全缓解率为53%(n=17例乳腺癌),晚期治疗组的客观缓解率>80%(n=71).
结论:接受测试的癌症患者中有三分之一携带PGV,约80%具有临床可行性。在现实世界中,四分之三的种系阳性晚期癌症患者接受了种系指导的治疗,强调种系测试在指导癌症治疗方面的实用性。